This is a renewal application from an experienced herpes virologist who proposes to study the molecular genetics of cytomegalovirus pathogenesis. During the previous five years of funding, the investigator identified several murine CMV genes which are dispensable for growth in cultured cells but play an important role in the host animal. In particular, the murine CMV protein sgg1 (which is dispensable in cell culture) has been shown to be required for efficient viral replication in the mouse salivary gland, but not in other organs. The first specific aim is to investigate the molecular and cellular basis of viral tropism for epithelial cells. In the second specific aim, the investigator will he will determine how IFNg and TNFa mediate immune clearance in salivary glands of murine CMV infected mice. The third aim is to determine the impact of pathogenesis of the C-C chemokine receptor (US28) encoded by human CMV on viral pathogenesis by transfer into the murine CMV genome.